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    Targeting intracellular protein traffic: new therapeutic strategies?

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    Team "Biology of phagocytes, infection and immunity" directed by Florence Niedergang

    Targeting intracellular protein traffic: new therapeutic strategies?

    Cell activity is related to protein synthesis and transport. Dysfunctions of these functions can lead to the development of pathologies or can promote infection by pathogens. A study published in Science Advances identifies, through a chemical library, molecules that disrupt this transport.

     

    The synthesis of new proteins and their transport to specific cellular compartments where they are active are essential functions for controlling cellular activity. Conversely, their dysfunction is often associated with the appearance of pathologies and/or the entry of pathogens into the body. Finding a way to specifically control or disrupt the transport of these proteins is therefore an important therapeutic issue. 

    Today, it is well established that many transport routes exist and it is therefore possible to specifically disrupt the transport of a protein involved in the development of a disease. 

    To go further and specifically monitor the transport of certain proteins in cells in culture, the team of Franck Perez, director of the Cell Biology and Cancer Unit UMR 144 (CNRS/Institut Curie), has developed a quantitative intracellular traffic analysis system (RUSH system) using pipetting robots and automated cellular imaging systems, coupled with image and date analysis algorithms, in order to screen large collections of chemical compounds (libraries) by automated cellular imaging with the help of the CurieCoreTech BioPhenics platform at the Institut Curie. 

    In collaboration with teams from Institut Cochin (Florence Nierdergang) and Institut Pasteur (Anne Brelot), small molecules inhibiting the transport of CCR5, the co-receptor for the Human Immunodeficiency Virus (HIV), to the cell surface have been identified. Their effects on HIV infection were studied in vitro. The authors reveal that inhibiting the secretion of CCR5 to the surface of primary human macrophages with these compounds partially protects them from HIV-1 infection. One advantage of these molecules is to block the secretion of CCR5 and not to prevent the virus from binding to its receptors. 

    This study demonstrates the possibility to specifically regulate certain intracellular transport pathways and opens up new avenues for therapeutic research based on cell biology.

     

    Reference

    Targeting CCR5 trafficking to inhibit HIV-1 infection. Boncompain G, Herit F, Tessier S, Lescure A, Del Nery E, Gestraud P, Staropoli I, Fukata Y, Fukata M, Brelot A, Niedergang F, Perez F. Science Advances, 2019, Vol. 5, no. 10, eaax0821.

     

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